Promoter hypermethylation profiling of distant breast cancer metastases
| Autor: | Cathy B. Moelans, Laura S. Jiwa, Paul J. van Diest, Willemijne A. M. E. Schrijver |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Oncology
Cancer Research Lung Neoplasms Skin Neoplasms Colorectal cancer PROGRESSION Metastasis COLORECTAL-CANCER Preclinical Study Breast cancer Hypermethylation Non-U.S. Gov't Promoter Regions Genetic CPG ISLAND Regulation of gene expression Aged 80 and over Brain Neoplasms Research Support Non-U.S. Gov't Liver Neoplasms METHYLATION Methylation Middle Aged Prognosis Primary tumor MLPA Gene Expression Regulation Neoplastic Distant metastases CpG site Lymphatic Metastasis DNA methylation Female SQUAMOUS-CELL CARCINOMA Adult medicine.medical_specialty Tumor suppressor genes Breast Neoplasms Biology Research Support RECEPTOR CONVERSION GENETIC-ANALYSIS Internal medicine medicine Journal Article Humans RNA Messenger Aged THERAPEUTIC TARGET Tumor Suppressor Proteins DNA Methylation medicine.disease MS-MLPA PRIMARY TUMORS |
| Zdroj: | Breast Cancer Research and Treatment Breast Cancer Research and Treatment, 151(1), 41. Springer New York |
| ISSN: | 0167-6806 |
| DOI: | 10.1007/s10549-015-3362-y |
| Popis: | Promoter hypermethylation of tumor suppressor genes seems to be an early event in breast carcinogenesis and is potentially reversible. This makes methylation a possible therapeutic target, a marker for treatment response and/or a prognostic factor. Methylation status of 40 tumor suppressor genes was compared between 53 primary breast tumors and their corresponding metastases to brain, lung, liver, or skin. In paired analyses, a significant decrease in methylation values was seen in distant metastases compared to their primaries in 21/40 individual tumor suppressor genes. Furthermore, primary tumors that metastasized to the liver clustered together, in line with the finding that primary breast carcinomas that metastasized to the brain, skin, or lung, showed higher methylation values in up to 27.5 % of tumor suppressor genes than primary carcinomas that metastasized to the liver. Conversion in methylation status of several genes from the primary tumor to the metastasis had prognostic value, and methylation status of some genes in the metastases predicted survival after onset of metastases. Methylation levels for most of the analyzed tumor suppressor genes were lower in distant metastases compared to their primaries, pointing to the dynamic aspect of methylation of these tumor suppressor genes during cancer progression. Also, specific distant metastatic sites seem to show differences in methylation patterns, implying that hypermethylation profiles of the primaries may steer site-specific metastatic spread. Lastly, methylation status of the metastases seems to have prognostic value. These promising findings warrant further validation in larger patient cohorts and more tumor suppressor genes. Electronic supplementary material The online version of this article (doi:10.1007/s10549-015-3362-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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